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Series GSE43475 Query DataSets for GSE43475
Status Public on Jan 07, 2014
Title UNRAVELING A NOVEL TRANSCRIPTION FACTOR CODE INDUCTIVE FOR THE HUMAN ARTERIAL-SPECIFIC ENDOTHELIAL CELL SIGNATURE
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Endothelial cells (EC) lining arteries and veins have distinct molecular and functional signatures. The (epi)genetic regulatory mechanisms underlying this heterogeneity in human EC are incompletely understood. Using genome-wide microarray screening we established a specific fingerprint of freshly isolated arterial (HUAEC) and venous EC (HUVEC) from human umbilical cord comprising 64 arterial and 12 venous genes, representing distinct functions and pathways. Among the arterial genes were 8 transcription factors, including HEY2, a downstream target of Notch signaling and the current ‘golden standard’ pathway for arterial EC specification. Short-term culture of HUAEC or HUVEC abrogated differential gene expression resulting in a default state. Erasure of arterial gene expression was at least in part due to loss of canonical Notch activity and HEY2 expression. Notably, nCounter analysis revealed that restoring HEY2 expression or Delta-like 4 (Dll4)-induced Notch signaling in cultured HUVEC or HUAEC only partially reinstated the arterial EC gene signature while combined overexpression of the 8 transcription factors restored this fingerprint much more robustly. Each transcription factor had a different impact on gene regulation, with some stimulating only few and others boosting a large proportion of arterial genes. Interestingly, although there was some overlap and cross-regulation, the transcription factors largely complemented each other in regulating the arterial EC gene profile. Thus, our study showed that Notch signaling determines only part of the arterial EC signature and identified additional novel and complementary transcriptional players in the complex regulation of human arteriovenous EC identity
 
Overall design To identify an arteriovenous (AV) fingerprint in human endothelial cells (EC) across different vascular beds, we used microarrays on RNA from 38 EC samples corresponding to 6 cultured human arterial-EC types (hepatic artery EC or HHAEC, N=3; aorta EC or HAEC, N=2; coronary artery EC or HCAEC, N=2; iliac artery EC or HIAEC, N=2; pulmonary artery EC or HPAEC, N=3; and umbilical artery EC or HUAEC-C, N=5), 4 cultured human venous-EC types (hepatic vein EC or HHVEC, N=3; iliac vein EC or HIVEC, N=3; pulmonary vein EC or HPVEC, N=2; and umbilical vein EC or HUVEC-C, N=5), freshly isolated HUAEC (HUAEC-F, N=4) and freshly isolated HUVEC (HUVEC-F, N=4). Due to the difficulty to obtain biopsies from healthy donors, we did not have access to freshly isolated aEC or vEC matched for all cultured EC types.
 
Contributor(s) Aranguren X, Agirre X, Segura V, Pascual-Montano A, Prósper F, Luttun A
Citation(s) 24108462
Submission date Jan 14, 2013
Last update date Mar 25, 2019
Contact name Xabier Agirre
E-mail(s) xaguirre@unav.es
Phone +34 948194700
Organization name CIMA
Department Oncology
Street address Pio XII, 55
City Pamplona
State/province Navarra
ZIP/Postal code 31008
Country Spain
 
Platforms (1)
GPL570 [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
Samples (38)
GSM1063374 HA1_7
GSM1063375 HA2_1
GSM1063376 HA3_2
Relations
BioProject PRJNA186526

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE43475_RAW.tar 185.1 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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